PAH role proposed for left heart failure biomarker

Levels of galectin-3 are elevated in patients with pulmonary arterial hypertension (PAH) and correlate with disease severity, research shows.

The findings published in Heart show that galectin-3 levels were elevated regardless of whether PAH was idiopathic (IPAH) or associated with connective tissue disease (CTD).

In a linked editorial, Bradley Maron (Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA) says that the currently used biomarkers for PAH - troponin-T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) - are surrogates for PAH symptoms, rather than reflecting the underlying process.

So these do not entirely address the clinical need, he says, explaining that "point-of-care risk stratification methods to guide initiation or escalation of treatment in PAH are limited currently to elaborate scoring systems that require invasive haemodynamic data, or metrics such as changes in 6-min walk distance and functional class that hinge on subjective assessment or are of controversial utility in clinical practice."

By contrast, galectin-3 is directly involved in the remodelling process that leads to heart failure; as such, it is gaining traction as a predictor of hard clinical outcomes in left heart failure.

In this study, average galectin-3 levels were 12.2 and 14.1 ng/mL in 41 patients with IPAH and 16 with PAH-CTD, respectively, which was significantly greater than the average 8.5 ng/mL found in eight healthy controls matched for age and gender.

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In left heart failure, elevated aldosterone levels lead to the release of galectin-3 from monocytes. But although aldosterone levels were significantly increased in IPAH patients relative to controls (248.5 vs 71.9 pg/mL), the increase in the PAH-CTD patients was not statistically significant (147.8 ng/mL).

This implies that galectin-3 is induced by other means, such as via inflammatory pathways, in patients with PAH-CTD, say researcher Georg Hansmann (Hannover Medical School, Germany) and colleagues.

"Interestingly, we did not find a direct correlation between plasma [galectin-3] and aldosterone in IPAH patients", they add. "Therefore, one might speculate that aldosterone-independent pathways are also relevant in IPAH-associated [galectin-3] upregulation."

Galectin-3 levels were associated with World Health Organization (WHO) functional class, being significantly higher in patients in classes II and III than those in class I.

The team also looked at NT-proBNP levels, finding that these were elevated in patients with IPAH and with PAH-CTD, and also correlated with WHO functional class. Several markers of vascular injury and inflammation were also upregulated in PAH patients, most notably intercellular adhesion molecule 1 in both PAH subgroups, and vascular cell adhesion molecule 1 and interleukin-12 in PAH-CTD patients only.

There have been clear statements from regulatory bodies that have increased the pressure on pharmaceutical companies to go electronic with their records and ensure a high level of data integrity in all areas of the pharmaceutical industry.

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